Chapter 10 FEMALE GENITAL TRACT TUMORS

Female genital tract tumors will be treated in each of the known anatomical segments: ovarian tumors;
oviductal tumors; uterine tumors; cervical tumors; and vaginal and vulvar tumors. Ovarian tumors are
relatively frequent in animals, especially in bitches, cows and mares, while the tumors of the other
anatomical segments of the female genital system (oviduct, uterus, cervix, vagina and vulva) have a
significantly lower incidence.

Histological Classification of Tumors of the Genital System of Domestic Animals (Kennedy et al.
1998)

Female

1. Tumors of the Ovary

1.1 Sex cord-stromal (gonadostromal) tumors

1.1.1 Granulosa cell tumor (granulose-theca cell tumor)

1.1.2 Thecoma (theca cell tumor)
1.1.3 Interstitial cell tumor (luteoma, lipid cell tumor, steroid cell tumor)

1.2 Germ cell tumors

1.2.1 Dysgerminoma
1.2.2 Teratoma
1.2.3 Embryonal carcinoma

1.3 Epithelial tumors

1.3.1 Papillary adenoma, papillary cystadenoma

1.3.2 Papillary adenocarcinoma
1.3.3 Rete adenoma

1.4 Mesenchymal tumors

1.4.1 Hemangioma
1.4.2 Leiomyoma

2. Tumors Metastatic to the Ovary

3. Tumorlike Lesions of the Ovary

3.1 Adenomatous hyperplasia of the rete ovarii

3.2 Papillary hyperplasia of the surface epithelium
3.3. Stromal hyperplasia
3.4 Vascular hamartoma

4. Cysts in and around the Ovary

4.1 Cysts in the ovary

4.1.1 Graafian follicle cysts

4.1.2 Luteinized cysts
4.1.3 Epithelial inclusion cysts in the mare (fossa cysts)
4.1.4 Cysts of the subsurface epithelial structures in the bitch
4.1.5 Cystic rete ovarii

4.2 Cysts around the ovary

4.2.1 Cysts of wolffian (mesonephric) tubules and ducts

4.2.2 Cysts of müllerian (paramesonephric) duct

5. Tumors of the Uterine Tube (Oviduct)

 5.1 Epithelial tumors

5.1.1 Adenoma
5.1.2 Adenocarcinoma

5.2 Mesenchymal tumors

5.2.1 Lipoma

6. Tumors of the Uterus

6.1 Epithelial tumors

6.1.1 Adenoma of the endometrium

6.1.2 Adenocarcinoma of the endometrium

6.2 Mesenchymal tumors

6.2.1 Fibroma
6.2.2 Leiomyoma
6.2.3 Leiomyosarcoma

7. Gestational Trophoblastic Disease

7.1 Subinvolution of placental sites in the bitch

8. Tumorlike Lesions of the Uterus

8.1 Adenomyosis of the uterus

8.2 Cystic endometrial hyperplasia
8.3 Endometrial cysts
8.4 Endometrial polyp
8.5 Lymphangiectasia
8.6 Wolffian (mesonephric duct cysts)
8.7 Serosal cysts

9. Tumors Metastatic to the Uterus

10. Tumors of the Cervix
11. Tumors of the Vagina and Vulva

11.1 Epithelial tumors

11.1.1 Papilloma
11.1.2 Fibropapilloma of cattle
11.1.3 Squamous cell carcinoma of the vulva
11.1.4 Urothelial carcinoma involving the canine vestibule

11.2 Mesenchymal tumors

11.2.1 Leiomyoma

11.3 Transmissible venereal tumor

12. Tumorlike Lesions of the Vulva and Vagina

12.1 Cysts
12.2 Edema of the vulva

10.1. TUMORS OF THE OVARY

Ovarian tumors have a higher incidence in bitches, then in cows, mares and ewes. Tumors are bilateral
in bitches, appearing in particular on the epithelial surface and in subepithelial structures. In cows,
ewes and mares, ovarian tumors are usually bilateral and are derived from the gonadal stroma, being
of granular cell type. There are few cases, reported by the literature, of ovarian tumors in felines and
swine. Ovarian tumors in cats are similar to those in dogs [3].

The majority of authors have adopted a simple, practical classification, correlated with the tumor
evolution based on the histological structure of the ovary, taking into consideration the pluripotency of
cell components and their histogenesis.

Classification of ovarian tumors:

1. epithelial tumors: papillary adenoma; papillary adenocarcinoma; cystadenoma; undifferentiated

carcinoma;
2. germ cell tumors: dysgerminoma; teratoma;
3. sex cord-stromal tumors: granular cell tumors; thecoma; luteoma;
4. connective tissue tumors;
5. secondary (metastatic) tumors;
6. unclassified tumors;
7. tumor-like lesions: adenomatous hyperplasia of the rete ovarii; papillary hyperplasia of the ovarian
serosae; vascular hamartoma; ovarian cysts.

10.1.1. Epithelial tumors

Epithelial tumors develop from the surface epithelium of the ovary, which is coelomic mesothelium. In
domestic animals, these tumors have a predominantly serous character and present a uniformity
regarding location, invasiveness, the mitotic index and morphology. Benign and malignant forms are
difficult to differentiate in most cases.

Epithelial tumors are frequent in dogs, less in other species, being similar to serous tumors in humans
[1]. In bitches, epithelial tumors represent 40–50% of all ovarian neoplasms [8]. Adenocarcinomas
represent 64%, of which almost half metastasize [9].

Papillary adenoma, papillary cystadenoma, is a frequently bilateral tumor, usually on the surface of the
ovary, developing from the surface epithelium, infiltrating as a tubular invagination in subepithelial
structures.

Microscopically, the tumor develops under a papillary and cystadenomatous form, having small
polygonal, cuboid or cylindrical cells, sometimes with cilia. The stroma is discrete but well
vascularized, being distributed around the cells ranged in a single layer, under a pseudoglandular
form, delimiting small spaces, irregular cavities, having a fluid protein content (Fig. 10.1).

Fig. 10.1
Papillary adenoma, ovary.

Cystadenoma has been diagnosed in dogs, being frequently found in association with cystic
endometrial hyperplasia. Papillary cystadenomas in bitches may contribute to the appearance of
ascites, by the secretion of tumor cells. Tumor formations develop bilaterally, with variable sizes: they
can be small, difficult to detect, or they may appear as irregular masses more than 10 mm in diameter.

Cystadenoma located in the ovarian bursa has a cauliflower-like aspect and frequently disseminates by
implantation in the peritoneum. The cystic aspect of the tumor is also maintained in section (Fig. 10.2,
10.3).
 Fig. 10.2
Cystadenoma.

Fig. 10.3
Adenoma of subsurface epithelial structures. Ovary. Bitch.

Papillary adenocarcinoma is a tumor frequently found in the canine ovary, usually bilateral, being
histologically similar to the benign form, papillary adenoma. The characteristics that differentiate the
malignant and benign forms are: tumor size; the mitotic index; invasion of ovarian stroma and
extension in the ovarian bursa, in the peritoneum, frequently with metastases by implantation. Cells
have a cuboid shape, lying on fine stromal septa, frequently with digital projections in the cystic
microcavities, having a clear or slightly pink protein content. More rarely, tumor cells contain mucin or
a squamous change (adenoacanthoma) [7] (Fig. 10.4, 10.5).

Fig. 10.4
Papillary adenocarcinoma, ovary.

Fig. 10.5
Papillary adenocarcinoma, ovary.

Undifferentiated carcinoma is a form of carcinoma composed of poorly differentiated cells whose type
is difficult to establish.

10.1.2. Germ cell tumors

Germ cell tumors originate from primordial ovarian germ cells, similar to testicular germ cells.
Embryonic carcinomas have not been described in animals. Dysgerminomas and teratomas have an
equal incidence in female dogs, and together they account for 20% of all ovarian tumors in this species.
Metastases represent 20–30%, with locations in abdominal viscera, lymph nodes, bones and lungs [1].

Dysgerminoma, which is also known as embryonic carcinoma, large cell carcinoma and ovarian
seminoma, is relatively frequent in dogs and cats, but much rarer compared to testicular seminoma,
being also diagnosed in cows and sows. It may have a uni- or bilateral location, it has a smooth surface
and soft consistency, and in section it is white-gray, with hemorrhagic or necrotic foci. Metastases are
found in 10–20% of cases, and hormone secretory activity is absent, generally appearing in old bitches.

Microscopically, the tumor is formed by a uniform cell population, large round or polygonal cells, with
poorly colored cytoplasm, similarly to seminoma. Nuclei are of variable sizes, vesicular, with 1–3
nucleoli, similar to spermatogonia. Giant cells and mitotic forms are frequently identified. Cells are
diffuse or arranged in islands or layers. The connective stroma is variable, but is frequently in a low
amount. Lymph node or perivascular formations are frequently noted, and large histiocytes, with clear
cytoplasm, occasionally appear (Fig. 10.6, 10.7.) [9, 10, 11].
 Fig. 10.6
Dysgerminoma.

Fig. 10.7
Dysgerminoma.

Teratoma has been rarely found in domestic animals, being reported in bitches, sows and mares. These
tumors are well differentiated and benign. A tumor thought to arise from totipotential germ cells that
have undergone somatic differentiation and given rise to two or more of the embryonic layers with a
variety of tissues being present [10] (Fig. 10.8).

Fig. 10.8
Teratoma.

Embryonal carcinoma, a germ cell tumor composed of embryonic multipotential cells that are capable
of further differentiation, producing a varied histologic pattern [10].

Normal tissues can be structurally identified along with neoplastic tissues, with solid and cystic areas,
containing sebaceous material and hair, sometimes skin, cartilage, bone, teeth and muscles, at other
times neural, adipose tissue or respiratory epithelium. A reasonable explanation for the appearance of
teratoma could be heterozygosity, as a result of meiotic division. Evidence for this is provided by a
number of biochemical and cytogenetic studies showing that ovarian teratoma tissues are unique, in
the sense that they are formed by XX diploid cells, but are homozygous in chromosomal loci for which
the host is heterozygous [3].

10.1.3. Sex cord-stromal (gonadostromal) tumors

Sex cord-stromal tumors are formed from the gonadal, medullary or cortical stroma, from granulosa
cells and theca interna cells. These neoplasms have the capacity to secrete hormonally active steroids
(estrogen and/or progesterone). The classification of sex cord-stromal tumors depends on the type
predominance and cell origin.

Sex cord-stromal tumors are common in cows and mares, and less frequent in bitches and ewes.
Incidence is higher in old cows and in cows under 4 years of age, or even calves. In mares, the mean
age is 9 years, between 7 and 16 years. No breed predilection has been found in any species.

Clinically, cows and mares with sex cord-stromal tumors may have an unchanged behavior or they can
present the signs of an oversecretion of estrogens and androgens. The manifestation of abnormal signs
can last for several months, one year or more. Mares manifest nymphomania or behave like stallions,
and cows have the same behavior. The behavior of animals with ovarian sex cord-stromal tumors is
deeply changed.

Estrus in these cows and mares is usually irregular, prolonged or absent, and animals are infertile.
Bitches show signs of hyperestrogenism, manifesting by cystic endometrial hyperplasia, prolonged
estrus, enlarged vulva and vaginal secretions. These clinical signs occur in approximately 50% of
bitches with sex cord-stromal tumors. In cats, the following have been noted: prolonged estrus, hair loss
and thinned pilose covering [6].
Macroscopically, in most cases in mares and cows, these tumors are unilateral, 10–23 cm in diameter.
They have an ovoid or spherical shape, they are lobulated, with a flaccid to dense consistency, usually
being encapsulated and limited to the ovary. Color is yellow-gray, with red bands and cysts that have a
watery, red-brown or yellow content. Necrotic and/or hemorrhagic foci frequently appear in section [4,
6].

Metastases have been found in mares, cats and cows, less in bitches. Granulosa cell tumors have a
higher malignancy compared to Sertoli cell tumors. Metastases in the peritoneum, large ligaments,
spleen, liver and lungs, lumbosacral, retroperitoneal and abdominal parenchymatous organ lymph
nodes have been found.

Granulosa-theca cell tumors or granulosa cell tumors have a benign character, they are unilateral,
incidence increases with age, but they have also been diagnosed in young animals.

Macroscopically, the tumor ranges between 4 and 16 cm in diameter, it has a soft to dense nodular
consistency. In section, dense areas, cysts and frequent hemorrhages and/or necroses are found, of
white-gray or yellow color. Some tumor forms produce steroids, which determines the appearance of
characteristic clinical signs, especially in cows and mares.

Microscopically, cells are similar to normal granulosa cells, appearing as a uniform population, with
poorly colored cytoplasm, poorly delimited, with round or ovoid eccentric nuclei, few or no mitoses
(Fig. 10.12 and 10.13).

Fig. 10.12
Granulosa cell tumor with luteinization.

Fig. 10.13
Granulosa - theca cell tumor.

Tumor cells can be arranged under the form of: diffuse sarcoma; long cords; islands delimited by
connective septa; follicles, in which cells may group forming spaces or foci with protein material,
similar to Call-Exner bodies from granulosa cells in humans [7].

In mares, these tumors are relatively frequent, and clinical manifestations consist of anestrus,
continuous and intermittent estrus, and male behavior. Affected animals have high plasma testosterone
levels. The ovary without tumor is atrophied.

The microscopic tumor is characterized by microcysts and prominent tubes, lined by double cell layers,
with basal ovoid nuclei. In some microscopic fields, structure is of follicular type. Some cells have
abundant, poorly colored cytoplasm, similar to testicular Sertoli cells, the connective stroma being well
represented in the tumor mass [3].

In cows, tumors formed by granulosa cells and Sertoli tumors are described. The incidence of these
tumors is lower in this species.

Neoplasms formed by granulosa cells have a microfollicular structure, with follicles of variable sizes,
lined by cells similar to follicular epithelium, to normal de Graaf follicle [6]. Cells are arranged in one,
two or more layers. The lumen of microfollicles contains acidophilic homogeneous or granular
material. Follicular cells can appear in the lumen, suggesting a cumulus oophorus aspect (Fig. 10.9), or
proliferations can be of papillary type, similar to a cystic papillary carcinoma. Tumor cells under the
form of solid masses or small rosettes have been noted, suggesting embryonic follicles. Neoplastic cells
are round or ovoid, fusiform, similar to normal follicular cells. Sizes are variable, with round or ovoid
hyperchromatic nuclei, the cytoplasm is vacuolated. Mitoses are present, sometimes in a high number.

Fig. 10.9
Granulosa - theca cell tumor.

Microscopically, neoplasms formed by Sertoli cells show a tubular or fascicular growth, with connective
septa. The cell cytoplasm is vacuolated, amphophilic staining. Cells have elongated shapes, frequently
with sharp tips, fusiform cells being exceptional. Nuclei are small, uniform, vesicular, nucleoli are
inapparent, mitoses are rare. Sertoli cell tumors, in animals, are not identical to those in women, in
which Leydig cells and immature mesenchymal structure also appear.

The origin of Sertoli cells in the ovary is explained by the common origin of female and male gonads,
from the same primordia.

In bitches, stromal ovarian neoplasms microscopically appear composed of three cell types: granulosa
cell tumors; Sertoli cell tumors; and non-specific gonadal tumors. In this species, these tumors coexist
with cystic endometrial hyperplasia and pyometra.

Granulosa cell tumors are composed of cells similar to developing follicles. Cells are round, with small
hyperchromatic nuclei, of variable sizes, and mitoses are numerous. Some cells are similar to Sertoli
cells, with foamy and poorly colored cytoplasm.

Sertoli cell tumors are formed by elongated cells, frequently with sharp tips, with foamy or clear
cytoplasm, with small uniform nuclei. Mitoses are in a low number. Cells are arranged in tubular
columns, bundles or clusters, separated by fine connective tissue septa (Fig. 10.10, 10.11).

Fig. 10.10
Granulosa - theca cell tumor. Sertoli-like tumor.

Fig. 10.11
Granulosa - theca cell tumor. Sertoli-like tumor.

Non-specific gonadal tumors are formed by cells similar to granulosa cells. Mitoses are rare and
anaplastic foci appear.

In cats, granulosa cell tumors are predominant. Cells are small, with eccentric hyperchromatic nuclei;
cells form microfollicles or Call Exner bodies with tumor cells arranged radially around eosinophilic
material. Mitoses and cellular atypias are obvious.

In this species, a tumor with lipid, round, uniform and well delimited cells can appear, some of which
are similar to Leydig cells [6].

Thecoma or theca cell tumor is exclusively composed of theca cells, which are fusiform or stellate, well
delimited, arranged in bundles. Nuclei are ovoid, elongated or fusiform, the cytoplasm is pale, with
lipid drops. Usually, thecoma is a benign tumor with expansive growth, without metastases [7] (Fig.
10.14).
 Fig. 10.14
Tecoma.

Luteoma is a rare tumor that has been reported in cows, female dogs and cats. Some authors consider it
to be similar to thecoma [3].

Macroscopically, the tumor is large, of yellow-brown color.

Microscopically, it is formed by a population of large, uniform lutein cells, similar to those of the corpus
luteum. Lipid cell tumors and Leydig cell tumors have been identified.

Lipid cell tumors are known in cats. Histologically, they are formed by large cells, loaded with lipids,
similar to those of the adrenal cortex, with small nuclei and well delimited margins.

Leydig cell tumors have a low incidence in domestic animals. Cells are uniform in shape and size,
polygonal, well delimited, with dark, granular cytoplasm, with numerous lipid vacuoles. Nuclei are
small, ovoid and hyperchromatic, with small nuclei and numerous mitoses. The connective stroma is
fine, with numerous capillaries, delimiting in some tumors pseudolobular forms.

10.1.4. Connective tissue tumors

Connective tissue tumors of the ovary are classified and have the characteristics known from the
chapter concerned. Hemangiomas and leiomyomas have a higher incidence.

Ovarian hemangioma is rare in domestic animals, except for swine. The tumor appears in adult and old
sows. Macroscopically, it has a globular, well circumscribed form, red-brown color, smooth surface,
with obvious superficial vascularization. The tumor develops in the ovarian cortex and occasionally it
can be bilateral. Microscopically, the tumor is composed of well differentiated endothelial cells, forming
capillaries with erythrocytes in the lumen. The connective tissue delimits vascular areas. No malignant
forms of these tumors have been reported.

Leiomyoma develops from the smooth muscle fibers of the mesovarium and has been reported in
bitches and sows. Rats treated with beta-adrenergic receptor stimulants have developed mesovarian
leiomyomas [3].

10.1.5. Metastatic tumors

Ovarian metastases of neoplasms from other tissues or organs are rare in domestic animals. Ovarian
metastases from breast carcinomas have been found in bitches, and uterine and intestinal carcinomas
in cows can metastasize in the ovaries. In female dogs and cats, metastases of pancreatic carcinomas
are reported in the ovaries [7].

10.1.6. Tumorlike lesions

Adenomatous hyperplasia of the rete ovarii is a rare lesion, which has been described in dogs. The
peripheral epithelium forms gland-like structures, located in the ovarian capsule. These lesions could
be considered preneoplastic, and their functional potential is not known.

Papillary hyperplasia of the ovarian serosa occurs as a result of prolonged estrogen stimulation. The
lesion appears bilaterally, with papillary proliferations on the ovarian serosa; it occurs in the bitch.

Stromal hyperplasia, the nonneoplastic proliferation of ovarian stroma; it is usually bilateral and
occurs in older animals [10].

Vascular hamartoma is a congenital abnormality that is rare in cows, sows and bitches. The lesion
appears as a vascular, arterial or venous malformation, in a connective tissue mass. Macroscopically, it
has large sizes, weighing several kilograms. Due to vascular thrombosis, edema, hemorrhage and
necrosis occur, followed by connective tissue proliferation. Small hamartomas are clearly delimited
from the ovarian tissue, but the ovarian mass is gradually incorporated. Differential diagnosis between
hemangioma and vascular hamartoma is difficult [3].

Cysts in and around the ovary. Cyst formation in and around the ovary in domestic animals is common.
In many cases, the lining cells degenerate and determining the origin of the cyst may be difficult.

Ovarian cysts frequently occur in domestic animals, especially in bitches, sows and cows. The
anatomical and histological structure of ovarian cysts is difficult to determine, requiring a thorough
examination and multiple sections in various areas, for microscopic examination.

Graafian follicle cysts can be solitary or multiple and are frequent in all species. They have a special
importance for cows and sows, in which they manifest by nymphomania. Cysts have a clear liquid, with
the presence of granulosa cells in the wall of small formations, and a single cuboid or flat cell layer in
large formations, sometimes granulosa cells being absent.

Luteinized cysts occur in mature follicles that have undergone the luteinization of the theca interna and
the total cysting of the luteal tissue line. These cysts have a spherical cavity, without projecting on the
ovarian surface, and are common only in the cow and sow.

Corpus luteum cysts appear after ovulation, but the follicle rupture surface closes prematurely and
blocks the fluid in the center of the corpus luteum. The ovular cavity is present and the cyst has an
irregular outline (Fig. 10.15).

Fig. 10.15
Corpus luteum cyst.

Rete tubules cysts are found in the majority of domestic animal species, frequently in dogs and cats. The
tubular network is located in the ovarian hilar region. Cyst growth induces the compression of the
ovarian cortex (Fig. 10.16 and 10.17).

Fig. 10.16
Surface epithelial cysts.

Fig. 10.17
Surface epithelial cysts.

Cysts around the ovary

Cysts of wolffian (mesonephric) tubules and ducts or paraovarian cysts are single or multiple, having
sizes that range from several millimeters to several centimeters in diameter. Locations are in the
mesovarian tissue or in the mesosalpinx. Cysts originating from the mesonephric ducts contain a clear
liquid and are lined by cuboid cells. Smooth muscle fibers surround the cysts. The anterior
mesonephric ducts have mesonephric remnants that frequently become cysts. These structures are
located in the lateral pole of the ovary adjacent to the fimbrial oviductal area. In mares, cysts are 6–8
cm in diameter [7] (Fig. 10.18).
 Fig. 10.18
Paraovarian cyst.

Cysts of müllerian (paramesonephric) duct, most are located near the fimbria of the uterine tube.

Surgical treatment is indicated in all ovarian tumors, ovariohysterectomy being recommended, since it
prevents the dissemination of neoplastic cells in the abdominal cavity. For malignant tumors, especially
when metastases have developed after excision and hormone treatment, prognosis, even reserved, is
difficult to predict [8].

In the case of cystadenocarcinomas, cyclophosphamide, chlorambucil and intracavitary bleomycin

treatment may be attempted. Good results can be obtained in the case of granulosa cell tumors, even
with metastases, by immunotherapy using mixed bacterial toxin [2].

10.2. TUMORS OF THE UTERINE TUBE (OVIDUCT)

Tumors of the uterine tube are rare in domestic mammals, but are not rare in chickens [10].

Oviductal tumors are extremely rare in all domestic mammalians; a moderate frequency is found in
chickens. Oviductal tumors have been reported in dogs, horses, cats, sheep, swine and cattle [5].

A classification of oviductal tumors includes the following forms:

1. epithelial tumors: adenoma and adenocarcinoma;

2. mesenchymal tumors: lipoma;
3. tumor-like lesions.

10.2.1. Epithelial tumors

Adenoma has been described in bitches, as a formation adjacent to the ovary; microscopically, papillary
proliferation with mature epithelium is detected, and in other areas, fibrous connective tissue with
smooth muscle fiber elements appears.

Adenocarcinoma has been reported in dogs, as an epithelial tumor with implantations in the
abdominal cavity. Histologically, the tumor is similar to adenoma.

10.2.2. Mesenchymal tumors

Lipoma is a rare oviductal tumor that is located in the ovarian bursa of dogs. The lipomatous mass has
the characteristics of mature adipose tissue.

10.2.3. Tumorlike lesions

The majority of domestic mammalians can have paramesonephric cysts, attached to the fimbriated end
of the salpinx. In large species, these formations can be several centimeters in diameter.

10.3. TUMORS OF THE UTERUS

Uterine tumors in domestic animals are uncommon, leiomyoma in cows and bitches, as well as uterine
carcinoma in cows being more frequent. The incidence of uterine tumors in domestic animals could be
higher, but systematic follow-up and the thorough examination of the uterus in the slaughter house and
on necropsy leaves to be desired. The classification of uterine tumors takes into consideration the
histological structure of this segment:

1. epithelial tumors: adenoma and adenocarcinoma;

2. mesenchymal tumors: fibroma; fibrosarcoma; leiomyoma; leiomyosarcoma; lipoma and lymphoma;
 3. unclassified tumors;
4. tumor-like lesions: adenomatosis, cystic endometrial hyperplasia; endometrial polyp;
lymphangiectasia; mesonephric duct cysts; serous cysts; subinvolutioned placental sites and squamous
metaplasia [5].

10.3.1. Epithelial tumors

Adenoma is a rare tumor that consists of discrete nodules, being a well differentiated endometrial
glandular tissue. The stromal and adenomatous component may exist in extremely various ratios, from
one subject to another. Sometimes, it may have a polyploid aspect, with proliferations in the uterine
lumen.

Adenocarcinoma of the endometrium is a neoplasm found in cattle and rabbits, being exceptionally
reported in other species (cats and dogs). It occurs in old cows, usually after the age of 7 years, being
difficult to diagnose clinically, except for cases in which the subject presents extensive metastases in the
lymph nodes and lungs.

Macroscopically, uterine carcinoma appears as single or multiple nodules, with a dense structure and
uneven distribution in the uterine wall, more frequently in the uterine horns, more rarely in the
cervical uterine corpus. The tumor infiltrates deep in the myometrium, without being in relation to
endometrial epithelium. The uterine wall is significantly thickened, sometimes it can reach 10 cm,
having an annular arrangement, which determines the significant narrowing of the lumen. The
umbilication of the serosa is mentioned, with an aspect characteristic of this neoplasm.

Microscopically, uterine carcinoma in cows has a scirrhous character, with infiltrative growth in the
myometrium, being intensely vascularized and with frequent muscle bundles. The tumor develops
from the deep uterine glands and is clearly distinguished from normal structures. The neoplasm is
formed by glands with irregular shapes and sizes, and cells are stratified and without polarity. Cells are
large, pleomorphic, with abundant cytoplasm, large, vesicular nuclei and numerous mitoses. The gland
lumen contains amorphous eosinophilic material. The stromal connective tissue has an aspect of
intense proliferation. The rate of metastases in lymph nodes and lungs is high. Lymph nodes, especially
iliac ones, are enlarged in volume, sometimes 10-fold larger than normal, having a bosselated surface
with numerous nodules. Lung metastases are usually bilateral, affecting all lobes; more rarely,
metastases are reported in the liver, visceral peritoneum or other viscera [6]. In dogs and cats,
adenocarcinoma is non-sclerotic, having a typical character of distinct proliferation in the
endometrium. The tumor is frequently well differentiated, with a glandular structure, formations with
a distinct lumen, lined by cylindrical cells, multinucleated cells also being noted. Fibrosis is present (Fig.
10.19 and 10.20).

Fig. 10.19
Uterine carcinoma, infiltration of muscularis.

Fig. 10.20
Uterine adenocarcinoma.

The factors that determine uterine carcinoma in domestic animals are little defined, and the
comparison to what is known in women proves the presence of special conditions in the latter case.
Prolonged estrogenicity, with cystic endometrial hyperplasia, represents precancerous lesions in
women, which induce the development of this neoplasm [8].
10.3.2. Mesenchymal tumors
Fibroma is a benign tumor, of hard consistency, white color, spherical or ovoid shape, located in the
uterine wall. Incidence is sporadic in bitches and cows, the tumor being frequently single, and more
rarely multiple. Microscopically, the tumor is formed by fibrous connective tissue.

Fibrosarcoma is a rare neoplasm in all domestic animal species, several cases have been reported in
cows, mares and bitches. The microscopic structure is that characteristic of fibrosarcoma described in
the chapter on connective tissue tumors.

Leiomyoma is a nodular tumor, of firm consistency, brown color, being reported in cattle and cats,
more frequently in dogs. In dogs and cats, 85–90% of uterine cases are estimated to be leiomyomas [8].
In bitches, the tumor appears at middle and old age, being frequently associated with ovarian follicular
cysts and also with endometrial hyperplasia, mammary hyperplasia and mammary neoplasm. Bitches
castrated at a young age do not develop leiomyoma, and in subjects with leiomyomas, the disease
regresses after castration. The administration of low estrogen amounts in female Guinea pigs induces
leiomyoma. In general, clinical evolution is asymptotic, sometimes it can be associated with vaginal
secretion or pyometra, and in the case of large tumors, it compresses the neighboring organs (intestines
or urinary tract) [3].

Macroscopically, leiomyoma can reach 10–12 cm in diameter, without being invasive. Initially, when
the tumor is small, it has a fleshy consistency, which becomes firm or even hard as it develops, hence
the term fibroid, due to stromal connective tissue. The section surface is wet, shiny, pink or white. The
tumor is not encapsulated, but is well delimited. In most cases, the tumor projects like a nodular tumor
into the uterine, vaginal or cervical lumen. The tumor may develop in two directions: the progressive
development of muscle tissue in a mass of fibrous connective tissue, or the appearance of edema and
liquefying and cysting of the tumor. In the first case, fibrosis progresses by hyalinization and
mineralization. In the second case, leiomyoma, especially vaginal leiomyoma, which is pedunculated
and poorly vascularized, degenerates.

Histologically, the tumor is formed by smooth muscle fibers, anarchically arranged in a mass of stromal
connective tissue. Muscle fibers can have a vortex arrangement, under the form of nests, being covered
with normal epithelium at the surface [3] (Fig. 10.22, 10.23).

Fig. 10.22
Uterine leiomyoma.

Fig. 10.23
Uterine leiomyoma.

Leiomyosarcoma is a rare neoplasm, being sporadically reported in cats, cattle, dogs and horses. The
macro- and microscopic characteristics are those known for leiomyosarcoma, but it is cellularized, with
large hyperchromatic nuclei and moderate mitotic index [5] (Fig. 10.24).

Fig. 10.24
Uterine leiomyosarcoma.
Lipoma is a rarely diagnosed tumor, being located at the site of insertion of large ligaments, in dogs.
Histologically, adipose cells are found. The transformation into liposarcoma has not been reported.

Malignant lymphoma is common in cows, more rarely in bitches, sows, mares and cats. The
microscopic structure is similar to lymphomas of other organs.

10.3.3. Tumorlike lesions of the uterus

Adenomyosis of the uterus refers to the presence of the endometrium in the myometrium. Endometrial
glands have a stromal support with large numerous blood vessels. The disease should not be confused
with endometriosis. This disorder has been noted in numerous laboratory monkey species. Sporadic
adenomyosis has been found in most species, but more frequently in cats, cattle and dogs. In the bitch,
it is often associated with cystic endometrial hyperplasia [10,11].

Cystic endometrial hyperplasia is the result of estrogen or progesterone stimulation. In sheep and
cattle, cystic endometrial hyperplasia is associated with estrogen stimulation, either from the ovary, or
by estrogen injections or accidental clover ingestion.

In bitches, three morphological types of endometrial hyperplasia are distinguished: the cystic
hyperplasia-pyometra complex, mainly induced by progesterone; cystic hyperplasia caused by certain
estrogenic compounds; false gestation (Fig. 10.21).

Fig. 10.21
Uterus cystic hyperplasia.

Diffuse patterns of cystic endometrial hyperplasia are produced in the cow, bitch and ewe by
hyperestrogenism. In the dog and cat, focal forms of endometrial hyperplasia are more common than
diffuse. The cells that line the cysts with papillary infolding and the nondistended glands as well as the
luminal surface are cuboidal to low columnar and have scant cytoplasm. There is only modest stromal
proliferation and usually no inflammation.

In sows and mares, cystic endometrial hyperplasia does not have a well established etiology [10,11].

Endometrial cysts may be the result of endometritis or hormonal stimulation, but the resultant cysts
may persist long after the initial cause has been removed. Small cysts are common adjacent to
caruncles in ruminants. Cystic endometrial glands are lined by flattened epithelium and surrounded by
varying amounts of fibrous connective tissue [10].

Endometrial polyps are focal endometrial proliferations with stromal elements of the endometrium,
found in dogs and cats. The stroma is frequently edematous.

Lymphangiectasia is a dilation of lymphatic vessels, in the ventral portion of the uterine corpus of old
mares; it also occurs in sows; focal areas of lymphangiectasia in the myometrium occur in the bitch and
cow.

Mesonephric duct cysts, which are remnants of these mesonephric ducts, can persist in the
endometrium and the myometrium, in almost all domestic animals. In dogs and cows, large cysts occur
in the uterine wall. Usually, epithelium is cuboid, with clear cytoplasm, the ducts being surrounded by
two muscle layers.

Serosal cysts are delimited from the peritoneum and appear on the uterine serosa in mature or old
cows and bitches. In bitches, they appear as prominent formations at antimesometrial uterine level,
while in cows they develop on the intercornual ligament.

Subinvolutioned placental sites. These lesions are more common in dogs, most of them around the age
of three years. Macroscopically, large placental adherence sites occur. Microscopy shows large cells
with eosinophilic cytoplasm in a connective mass, infiltration of plasmacytes, lymphocytes and
macrophages with hemosiderin. Numerous eosinophils invade the myometrium.

Squamous metaplasia appears on the surface of the endometrium, occasionally in pyometra cases, in
most domestic species. Sometimes, the endometrium can change into squamous type epithelium.

Tumors metastatic to the uterus are common in lymphoma in cattle, less so in horses; they are rare in
other species; serosal implantations do occur in peritoneal carcinomatosis [10].

10.4. CERVICAL TUMORS

In general, cervical tumors are identical to uterine neoplasms. These are: fibroma, leiomyoma, sarcoma
and unclassified tumors.

Tumor-like lesions at the level of the cervix mainly include: epithelial cysts; fibrosis and squamous
metaplasia.

10.5. TUMORS OF THE VAGINA AND VULVA

Vaginal and vulvar tumors are morphologically similar to penile and uterine tumors. The classification
of vaginal and vulvar tumors includes the following types:

1. epithelial tumors: papilloma (transmissible genital papilloma in pigs);

2. fibropapilloma;
3. leiomyoma;
4. canine transmissible venereal tumors;
5. malignant lymphoma;
6. fibrosarcoma;
7. vascular tumors;
8. malignant melanoma;
9. unclassified tumors;
10. tumor-like lesions; Gartner duct cysts; Bartholin gland cysts; granular vaginitis; herniated adipose
tissue; estrous vulvar edema.

10.5.1. Epithelial tumors

Papilloma is a rare benign tumor, with a papilliform proliferation aspect, having the connective stroma
covered by keratinized epithelium. It is usually small, but sometimes it may have large sizes. The
papilloma implantation base is infiltrated with lymphoplasmacytes. The tumor is induced by a
venereally transmitted virus that appears in swine.

Transmissible genital papilloma in pigs appears in the preputial diverticulum of the boar. The lesion
can be experimentally reproduced by the scarification of the vulvar mucosa.

The lesion can be transmitted by the sexual act to sows and it has sizes between 1 and 3 cm, a papular
aspect; sometimes, lesions are larger, being of papillary type. Clinical evolution may last for several
weeks, after which the lesion starts to regress or desquamate. The animal is immune to reinfection.

Microscopically, it has a typical papillomatous character, with extensive uneven acanthosis of the
covering epithelium, with a weak mesodermal reaction. The thickened malpighian layer contains
dispersed cells with intracytoplasmic inclusions. Inclusions are large, spherical, homogeneously
acidophilic, surrounded by a halo. An infiltration with mononuclear cells is found at the base of the
tumor in the dermis [3].

Squamous cell carcinoma is almost exclusively found in cows, but it has also been described in sheep
exposed for a longer time to solar radiation, also in mares and bitches.

Macroscopically, the neoplasm is identified on the vaginal mucosa or at the junction of the vulvar
mucosa with the skin, appearing almost exclusively in the unpigmented vulva or vulvar areas. In
section, nodules or firm bundles of homogeneous tissue are detected, of yellow or gray color, with
necrotic and/or hemorrhagic foci, separated by fibrous white-gray bands of stromal connective tissue.
Depending on the intensity of keratinization, the neoplasm can have a soft, firm, dry or wet consistency.

Histological structure is different depending on the carcinoma stage. In the early stage, the horny layer
shows a thickening under the form of foci, the granular layer is non-uniform, and the spinous layer
cells become more elongated and sharp. The dermal connective tissue is less dense and slightly
edematous, being intensely vascularized, with slight eosinophilic and lymphocytic infiltration.
Sebaceous glands are large and more active, compared to normal areas.

In the acanthotic stage, hyperkeratosis is moderate; the spinous cell layer is hyperplastic, with large
irregular cells, hyperchromatic nuclei and pale cytoplasm. Basal cells have an irregular palisade
arrangement, and are round. Dermal papillae are intensely vascularized, with eosinophilic and
lymphocytic infiltration. Sebaceous glands are large and active, some of them being cystic.

The tumor grows similarly to papilloma, with marked acanthosis. The early carcinoma develops in
acanthotic and papillomatous areas, under the form of foci formed by round or oval cells, with pale
cytoplasm, poorly evidenced outline, large nuclei of various sizes. The general aspect is of
malignization, with a spiral cell arrangement. A penetration of the significantly elongated spinous cells
gradually appears, and the basal layer cells are irregularly arranged in palisades. Epithelial buds
develop from cells that no longer resemble the cells of origin. Keratinized cells appear under the form
of epithelial pearls, and peripheral cells from these epithelial buds proliferate and infiltrate in all
directions.

Vaginal squamous cell carcinoma finally has all the growth and structural characteristics of squamous
cell carcinoma developed in other skin areas. In the depth and around carcinomatous cells, a fibrous
stroma with lymphocytic infiltration develops.

Vulvar squamous cell carcinoma metastasizes in regional lymph nodes and lungs [6].

10.5.2. Fibropapilloma of cattle

Vulvar fibropapilloma is a benign tumor, common in young cattle. Bovine papillomavirus is
incriminated in the etiology of the tumor, which causes the appearance of papillomas, with a relative
growth of the connective tissue and a marked thickening of the epidermis. The tumor can be
transplanted from the vulva to the penis and vice versa.

Macroscopically, tumors are usually sessile, initially round, then they gradually become cauliflower-like
or fungoid, less than 3 cm in diameter, with a large implantation base. Large tumors are frequently
ulcerated or they bleed. Spontaneous regression seems to be frequent, extending over a period of 1–6
months or more. There are occasional tumor recurrences after excision.

Microscopically, the tumor is formed by bundles of fibroblasts and epithelial proliferations that develop
in the fibromatous mass. In early tumor growth, numerous mitotic figures are found, which makes
difficult the differentiation from fibrosarcoma. There are numerous fusiform cells with large nuclei,
bizarre nucleoli, and pale eosinophilic intranuclear inclusions some-times appear. Stromal collagen
formations gradually develop into fibrosis. In the case of superficial ulcerations, inflammatory reaction
appears [3, 5].

10.5.3. Vulvar leiomyoma

Vulvar leiomyomas are benign nodular, whitish and firm tumors, being common in dogs. These tumors
are formed by bands of smooth muscle fibers that alternate with collagen bundles.

10.5.4. Transmissible venereal tumors

Transmissible venereal tumors are formed by diffuse or nest-like submucosal cell masses that extend in
the generating layer of the mucosa. The surface epithelium is frequently hyperplastic and sometimes
ulcerated. The trabecular connective tissue contains congested blood vessels that traverse the
neoplastic mass. Neoplastic cells have a low density, the cytoplasm is poorly delimited, oval or round,
eosinophilic, with large round to oval nuclei, mitotic figures are common. Chromatin is fine, dispersed,
with visible nucleoli, and mitoses are frequent. In some tumors, lymphocytes and plasmacytes are
present, in others they are absent, eosinophilia is found in many neoplasms. Metastases are not a rule,
but they can be found in regional lymph nodes (Fig. 12.4. and 12.5.).

Spontaneous regression is frequently found 2 months after onset. Transmissible venereal tumors of the
vagina are identical to those found in males.

10.5.5. Sporadic vaginal and vulvar tumors

Malignant lymphoma is frequent in cattle, and rare in dogs, swine and cats. Its structure and behavior
are identical to those of the malignant lymphoma of the hematopoietic tissue and lymph nodes.

Fibrosarcoma is a rare tumor in the majority of domestic animals, some cases being reported in cows,
mares and bitches. Morphologically, the neoplasm has all the characteristics of connective tissue
fibrosarcoma presented in the chapter concerned.

Vascular tumors, such as hemangioma and hemangiosarcoma, are rare at this level and they
morphologically correspond to the types described for connective tissue neoplasms.

Melanoma and melanocytoma are tumors that are found in particular in white mares, under the form
of large ulcerated nodules, located in the vulva or the perineum.

Unclassified tumors are proliferative formations that cannot be included in the categories mentioned
and described in the previous chapters.

10.5.6. Tumorlike lesions

Gartner duct cysts are in general extremely rare in virgin females; in contrast, they can be frequently
diagnosed in multiparous females, in which vaginal infections are also found.

Bartholin gland cysts occur post-inflammation and they can be associated with ovarian cysts in the cow.

Granular vaginitis is a common disease in cows, with the involvement of submucosal lymphoid
follicles, appearing under a nodular form in the vaginal and vulvar mucosa.

Herniated adipose tissue is found in excessively fat cows, at the junction between the vulva and the
vagina. It appears as an adipose perineal mass, which projects in the lumen of the genital tract.

Estrual edema of the vulva appears in the subepithelial connective tissue of bitches, with a diffuse
aspect. Fibrosis develops in chronic evolution. In swine, ingestion of an estrogenic mycotoxin,
zearalenone, which is produced by fungi of the genus Fusarium, causes congestion and edematous
swelling of the vulva and vagina.

BIBLIOGRAPHY
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[PubMed: 2984828]
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3. Kennedy PC, Miller RB. The Female Genital System. In: Jubb, Kennedy, Palmer, editors. Pathology of
Domestic Animals. Academic Press; New-York: 1993. pp. 349–470.
4. Madewell BR, Theilen GH. Tumors of the Urogenital Tract. In: Theilen, Madewell, editors. Vetrinary
Cancer Medicine. Lea & Febiger; Philadelphia: 1987. pp. 583–600.
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6. Moulton JE. Tumors of the Genital System in Tumors in Domestic. Animals, Univ. California Press;
Berkeley: 1978. pp. 309–345.
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1976;53:203–215. [PMC free article: PMC2366495] [PubMed: 1086151]
8. O’Keefe DA. Tumours of the Genital System and Mammary glands. In: Etinger, Felman, editors.
Veterinary Internal Medicine. Vol. 2. W.B. Saunders Company; Philadelphia: 1995. pp. 1699–1704.
9. Patnaik AK, Greenlee PG. Canine ovarian neoplasms: A clini-cipathologic study of 71 cases, including
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10. KENNEDY PC, CULLEN JM, EDWARDS JF, GOLDSCHMIDT MH, LARSEN S, MUNSON L, NIELSEN S.
Histological Classification of Tumors of the Genital System of Domestic Animals. Second Series. VI.
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List of Figures 10.1-10/24

Fig. 10.1 Papillary adenoma, ovary. *)
Fig. 10.2 Cystadenoma. *)
Fig. 10.3 Adenoma of subsurface epithelial structures. Ovary. Bitch.
Fig. 10.4 Papillary adenocarcinoma, ovary. *)
Fig. 10.5 Papillary adenocarcinoma, ovary. *)
Fig. 10.6 Dysgerminoma. *)
Fig. 10.7 Dysgerminoma. *)
Fig. 10.8 Teratoma. *)
Fig. 10.9 Granulosa - theca cell tumor. *)
Fig. 10.10 Granulosa - theca cell tumor. Sertoli-like tumor.
Fig. 10.11 Granulosa - theca cell tumor. Sertoli-like tumor.
Fig. 10.12 Granulosa cell tumor with luteinization. *)
Fig. 10.13 Granulosa - theca cell tumor.
Fig. 10.14 Tecoma. *)
Fig. 10.15 Corpus luteum cyst. *)
Fig. 10.16 Surface epithelial cysts. *)
Fig. 10.17 Surface epithelial cysts. *)
Fig. 10.18 Paraovarian cyst. *)
Fig. 10.19 Uterine carcinoma, infiltration of muscularis. *)
Fig. 10.20 Uterine adenocarcinoma.
Fig. 10.21 Uterus cystic hyperplasia. *)
Fig. 10.22 Uterine leiomyoma. *)
Fig. 10.23 Uterine leiomyoma.
Fig. 10.24 Uterine leiomyosarcoma.

Footnotes
* Courtesy of W.H.O.

Publication Details

Copyright
Copyright © 2007, The Publishing House of the Romanian Academy.

Publisher
The Publishing House of the Romanian Academy, Bucharest (RO)

NLM Citation
Baba AI, Câtoi C. Comparative Oncology. Bucharest (RO): The Publishing House of the Romanian Academy; 2007. Chapter 10, FEMALE
GENITAL TRACT TUMORS.